A More Sensitive Blood Test to Diagnose Heart Disease: the Dawn of a New Era?

Heart attacks are a major cause of illness and death in the United States. According to 2013 Center for Disease Control and Prevention estimates, about 116,793 people die of a heart attack every year in the United States. Someone has a heart attack every 43 seconds in the United States. In medicine, doctors often use the phrase "time is muscle" to emphasize the importance of rapid diagnosis and treatment of a heart attack. The meaning is simple: The longer we wait, the more damage the heart muscle suffers, and the lower the chances of excellent recovery.

With this in mind, substantial efforts have been made to speed up the diagnosis of heart attack. One example of these efforts is the continued advancements in lab testing technology that recently led to the development of a much more sensitive and precise test for measuring heart proteins, such as cardiac enzymes or troponin, released into the bloodstream.

In current clinical practice, a heart attack is diagnosed by a combination of clinical symptoms, electrocardiographic changes and a blood test. The blood test measures cardiac troponin levels. These structural proteins are integral components of the heart muscle and are released into the bloodstream only in the event of damage to the heart muscle. Cardiac troponins rise in the blood the first two to three hours after a heart attack starts. The older, more traditional versions of this test were used for many decades to assess heart injury or attack.

While the traditional troponin blood tests are highly specific -- meaning they rarely result in a false positive -- they have a lower sensitivity, which can result in some false negative results when the blood test appears normal but the person is in fact having a heart attack. Therefore, it is recommended to repeat traditional cardiac troponin measurements a number of times over 12 to 24 hours to overcome this limitation. This repeated testing delays the diagnosis of heart attack with consequent delay in appropriate treatment. It also prolongs unnecessary inpatient stays for those who do not have a heart attack, not to mention the need for additional expensive testing, such as stress tests and CT X-rays of the heart.

Thankfully, these problems may now become a distant memory with the development of new high-sensitivity troponin blood tests. These tests are already approved for use in Europe and should be approved in the United States in the near future.

What is high-sensitivity cardiac troponin?

High-sensitivity cardiac troponin blood tests have the ability to detect the same heart protein that is measured by the traditional tests, just in far lower concentrations. These tests can measure levels of troponin that are over 10 times lower than the limit of detection for the currently used traditional troponin blood test.

Can high-sensitivity cardiac troponin be used to diagnose heart attack in the emergency department?

Chest pain accounts for about 5 million visits to the emergency department each year in the U.S. Although chest pain is a major symptom of a heart attack, it can also be completely unrelated to the heart. In fact, only about 5 percent of all emergency department visits for chest pain are due to heart attacks.

Based on increased precision, high-sensitivity cardiac troponin blood tests offer the advantage of diagnosing a heart attack earlier and faster as compared to their traditional counterparts. This provides doctors and other health care providers with the advantage of being able to provide timely and appropriate care to their patients. Additionally, it obviates the need for long hours of waiting, as is often required with the traditional troponin blood tests currently used to rule out heart attacks. These new tests reliably rule out heart attack about 95 percent or more of the time when measured at patient admission. Though much improved in comparison to the traditional tests, it still leaves about 5 percent of cases that could potentially be missed. Reassuringly, several studies have shown that the sensitivity of these tests increases by 99 to 100 percent when a repeat measurement is performed three to six hours after patient admission for chest pain.

But the downside is that there can be an increase in false positives with these new high-sensitivity tests. This limitation is critical in the emergency room, where such false positives could lead to unnecessary invasive measures, like coronary angiography. Therefore, rather than ruling in a heart attack, this new blood test can be better used to quickly rule out heart attack -- a feature that could reduce unnecessary hospitalization and costly testing. For example, in a recent study of about 6,000 patients evaluated in the emergency room for suspected heart attack, physicians used a high-sensitivity cardiac troponin test to identify the almost two-thirds of patients who were at very low risk of having a heart attack and could be safely discharged.

Nonetheless, this exquisite sensitivity comes with the responsibility of understanding the interpretation of positive results. Not all troponin in the bloodstream can be assumed to be due to a heart attack. It's clear that elevation in troponin level signifies injury to heart tissue, but this does not help define the underlying cause of this injury. For example, some degree of heart tissue damage -- and thus, troponin elevation -- can occur in severe infection, kidney failure or when blood oxygen is low. With the advent of these new tests, it will be more important to take into account the patient's history, physical exam and risk assessment in combination with troponin measurements to guide diagnosis and rule in decisions of heart attack to optimize treatment.

Can adults without known heart disease or symptoms test positive for high-sensitivity cardiac troponin?

Yes. Many studies discovered that apparently healthy individuals in the community without known heart disease who weren't having any symptoms, like chest pain, tested positive using the high-sensitivity troponin test. This is important, as elevated troponin levels detected with the new tests are associated with future heart and blood vessel disease events, such as death from coronary heart disease, heart failure and death from any cause.

In the Atherosclerosis Risk in Communities Study of middle-age to older American adults, the researchers showed high troponin levels with the new tests in 67 percent of individuals without pre-existing heart disease -- the vast majority of whom would have not been identified with the use of currently available troponin assays. These results were similar to two other population studies, the Cardiovascular Health Study and the Dallas Heart Study. All three studies used the same troponin test.

Collectively, these studies suggest that these new tests could potentially be used for risk prediction and provide valuable prognostic information to prevent heart disease. Therapies, such as cholesterol-lowering statins or blood-thinning aspirin, could be considered for individuals classified as higher risk for heart disease by means of high-sensitivity troponin blood tests. However, because abnormalities with this test are so common and further is research needed, precise recommendations from professional committees, such as the American Heart Association, will be required to guide the clinical care of asymptomatic individuals with elevated troponin levels when these tests are used as a risk prediction tool.

Is the high-sensitivity cardiac troponin test available in the United States?

The high-sensitivity cardiac troponin tests -- both cardiac troponin T and I -- have been available and widely used in other countries, including in Europe, for five or more years. There are several contemporary tests available only for experimental use in the United States. It is presumed that these will soon be available for clinical use, hopefully within a year or two, pending approval by the Food and Drug Administration.

Several studies conducted in Europe compared these new tests with conventional tests for heart attack diagnosis. These studies showed the advantage of these new tests in early heart attack detection and in safely ruling out symptomatic patients, especially in the first three to six hours, which led to incorporating these tests into clinical guidelines for European countries. As mentioned above, the clinical implications of elevated troponin levels in a healthy population are still under investigation.

What are the future challenges?

Doctors are likely to face myriad challenges with the anticipated approval of the novel tests. Determining how to address false positives with this new test and where the patient has heart muscle damage unrelated to a heart attack will be important next steps. Nonetheless, the anticipated upcoming application of these new tests into clinical practice will necessitate a change in the algorithm of heart attack diagnosis because of our enhanced ability to detect them earlier using these tests, which could shorten the observation time in emergency rooms dramatically. Moreover, the use of these novel tests as a screening tool for heart disease risk prediction is very attractive, but additional research is required before they can be used as a widespread screening strategy. If appropriately used, these tests will help advance clinical care to a new era.

Dr. Nidhi Madan is currently a resident in internal medicine at Jacobi Medical Center, Albert Einstein College of Medicine, and she is pursuing a Masters in Public Health at the Johns Hopkins University Bloomberg School of Public Health. Her research interests are focused on cardiovascular disease epidemiology, particularly preventive cardiology.